Objective To use mimicry epitopes from phage displayed peptide library as substitute for recombinant human cyclophilin A (rhCyPA) in detection of CyPA autoantibody in sera of patients with systemic lupus erythematosus (SLE).Methods Monoclonal antibody D4 and E6 were used as the capture antibody; the Ph.D.-12 p hage display peptide library was screened by biopanning. Ten phage clones with h igh affinity for McAb D4 and E6 (five for each) were chosen. Their inserts were sequenced. The amino sequence of mimicry epitope was subsequently reasoned out. Selected 12 peptide and previously obtained 7 peptide mimicry epitopes were used as coated antigen and compared with rhCyPA in ELISA for anti-CyPA autoantibody .Results Nine of ten phage clones with high affinity for McAb D4 and E6 (five for D4, four for E6) shared a consensus amino sequence HW EYTTSPHPRL. In comparative study of ELISA, 56 serum samples from SLE patients we re tested for anti-CyPA autoantibody, 28 samples were positive (50%) with 12 pe ptide mimicry antigen and 24 were positive (43%) with rhCyPA, 4 of 34 (11%) samp les from those with other autoimmune disorders were positive with both antigens, the coincidence rate between two methods was 95 6%. The research also showed t hat 12 peptide mimicry antigen has the advantages of rhCyPA and 7 peptide mimicr y antigen in detecting anti-CyPA autoantibody. Conclusions The specific 12 peptide screened from phage-displayed peptide library by ant i-CyPA monoclonal antibody can mimic epitope information of cyclophilin A well and be used as substitute for rhCyPA in ELISA.

Objective To explore the cause, clinical characteristic and the relation to the alterations of bone metabolism and bone mineral density (BMD) in senile male patients with chronic obstructive pulmonary disease (COPD). Methods Fifty senile male patients with simple stable COPD were divided into moderate and severe groups based on the diagnostic criteria of pulmonary function. Thirty senile male health volunteers were considered as control group. Blood gas analysis, BMD, bone mineral content (BMC), biochemical indexes relative to the bone formation and bone absorption in blood and urine were measured and analyzed. Results Reductions in BMD and BMC were more significant in two COPD groups than those in control group (P

OBJECTIVE:To study the protective effects of Baimai ointment on sciatic nerve injury in rabbit. METHODS:The rabbit sciatic nerve injury model was induced by forceps operation. 180 rabbits were randomly divided into 6 groups,with 30 rab-bits in each group (10 rabbits of 7,14,28 d),including sham operation group (blank matrix of Baimai ointment for external use),model group(same as sham operation group),positive group [ig Mecobalamine tablet solution 1.25×10-4 g/(kg·d)] and Bai-mai low-dose,medium-dose and high-dose groups [Baimai ointment 0.33,0.67 and 1.34 g/(kg·d)for external use],once a day, for consecutive 7,14 and 28 d. Gait instrument was used to test the foot-touch-land force of rabbit;pathology examination was conducted for sciatic nerve resection;immunohistochemistry was used to detect the levels of NOS and NMDA in nerve tissue. RE-SULTS:Baimai ointment can significantly relieve sciatic nerve injury,edema and inflammatory reaction;7,14 and 28 d after med-ication,compared with model group,foot-touch-land force decreased significantly in rabbits with sciatic nerve injury (P<0.01);14,28 d after medication,foot-touch-land force of rabbits increased significantly in positive group,Baimai ointment groups,while the levels of NOS and NMDA decreased in nervous tissue(P<0.05). CONCLUSIONS:Baimai ointment can protect sciatic nerve with function injury in rabbits.

Objective To investigate the effect of olmesartan medoxomil on osteoprotegerin and serum inflammatory factor expression in atherosclerosis model rat.Methods From 2015 April in Jiangsu Institute of schistosomiasis control,24 Sprague-Dawley rats were randomly divided into the following three groups:the control group was fed with standard food,the model group was fed with high fat diet based on standard food(normal food +2％ cholesterol +5％ goat fat +0.2％ acid +7×105 IU/(kg·d) Vitamin D3),and the olmesartan group was given 3 mg/(kg·d) olmesartan gavage daily on the basis of high fat diet.On the fourth week of experiment the level of serum high sensitivity C reactive protein and serum lipids include total cholesterol,low density lipoprotein,high density lipoprotein and triglyceride were detected.The structure and changes of aortic pathology was observed.The expression of osteoprotegerinin in aortic was detected by immunohistochemistry staining and Western blot.Results Within the model group,the level of serum lipid and high-sensitivity C reactive protein increased significantly,endometrial thickness,intima-to-media thickness ratio and osteoprotegerin expression in aorta was significantly higher than that of normal group,the difference was statistically significant(P<0.05).The serum high density lipoprotein increased significantly,the level of other serum lipids and high sensitive C reaction protein decreased significantly,endometrial thickness,intima-to-media thickness ratio and osteoprotegerin expression in aorta of the olmesartan treated rats were significantly lower than those of model animals,the difference was statistically significant(P<0.05).Conclusion Olmesartan may suppress the development of atherosclerosis in model rats by decreasing the expression of osteoprotegerin and the level of serum inflammatory cytokines.

Objective To explore the clinical manifestations of hypermastigote detected from bronchoalveolar lavage fluid in children with mycoplasma pneumoniae pneumonia (MPP).Methods The clinical data from 18 cases (7 male cases,11 female cases;the age raged from 5 months to 13 years;13 case lived in rural cottage,5 cases lived in town building;the course ranged from 2 to 60 days) of MPP coinfected with hypermastigote were retrospectively analyzed,including the symptomatic and physical examination data, laboratory test, chest imaging features, bronchoscopic manifestation imaging,treatment and prognosis.The clinical characteristics and treatment of MPP coinfected with hypermastigote were analyzed.Results Clinical symptoms showed that 18 cases had cough, 14 cases had fever and 4 cases had asthma;laboratory blood routine test detected that 13 cases had increased leukocytes,5 cases with increased eosinophils;11 cases with increased C reactive protein and 8 cases with increased erythrocyte sedimentation rate.Eleven of 18 cases received immunological examination,which showed that 3 cases had increased IgG,2 cases with increased IgM,5 cases with increased IgA,and 11 cases with decreased ratio of CD4 and CD8;bronchoalveolar lavage fluid test showed that 1 case had increased eosinophils and hypermastigote were detected in 18 cases.High density spotty shadow were seen in chest imaging.Mucosal congestion, attached with white sputamentum, longitudinal folds, floc floating and sputum bolt obstructing within the lumen were seen under the bronchoscopy.The macrolides antibiotics combined with metronidazole (5 cases received metronidazole lung lavage) were effective.Conclusions Hypermastigote is a new type pathogen isolated from the lower respiratory tract in Liaocheng.For patients with MPP who have unsatisfactory response, hypermastigote should be taken into account and combined with metronidazole in therapy for better effect.

OBJECTIVE: To study the clinical and sequence character of the entire mitochondrial genome in five subjects with mitochondrial 12SrRNA T1095C mutation, and to analyze its relationship with the military noise-induced hearing loss (NIHL). METHOD: Three hundreds and four soldiers exposed to military noise were selected in Yunan and Beijing, including susceptible (experimental) and tolerance (control) groups. Mitochondrial 12SrRNA T1095C mutation were found in 5 subjects. Then the complete nucleotide sequence of five subjects were sequenced and its clinical character were analyzed. RESULT: m12SrRNA T1095C mutation were identified in 5 subjects of experimental group,and none were found in control group. There was significant difference between them (P < 0.05). All five soldiers had the history of military noise exposure and showed sensorineural deafness of different degrees. Sequence analysis of the complete mitochondrial genomes showed the distinct sets of mtDNA polymorphism besides T1095C mutation in five subjects. CONCLUSION The T1095C mutation in hearing loss subjects with various genetic background and history of military noise exposure, is involved in the pathogenesis of hearing impairment. It indicates that the T1095C mutation do relate well with military noise induced-hearing loss.
Adult ; Base Sequence ; DNA, Mitochondrial ; genetics ; Hearing Loss, Noise-Induced ; genetics ; Humans ; Male ; Military Personnel ; Mutation ; Young Adult

OBJECTIVE: To observe the changes of blood pressure and S-100B, neuron specific enolase (NSE) protein in hypertensive dogs with high fat diet after catheter-based renal sympathetic denervation. METHODS: Twelve Beagles were divided into an interventional group (n=6) and a sham-operation group (n=6). After baseline measurements, the Beagles were fed with lard oil for 3 months. After 3 months, the interventional group had renal sympathetic denervation by percutaneous catheter based radiofrequency ablation and the control group had renal angiography. The blood pressure, plasma S-100B, and NSE before the operation and 3 days, 1 week, 2 weeks, 1 month, 2 months and 3 months after the operation were measured. RESULTS: The dogs had significantly higher levels of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MBP) compared to its baselines (P<0.05). The SBP, DBP and MBP in the interventional group were significantly lower than those in the control group 1 month and 3 months after the operation (P<0.05). Three months after the operation, renal angiography in all dogs revealed no sign of renal artery stenosis. Plasma S-100B and NSE expression in the interventional group were higher than those in the control group 3 days, 1 week and 2 weeks after the operation (P<0.05). CONCLUSION Renal sympathetic denervation can significantly reduce the SBP, DBP and MBP in hypertensive dogs. The plasma S-100B and NSE may be used as indicators for assessment of renal nerve injury after renal sympathetic denervation.
Animals ; Blood Pressure ; Catheter Ablation ; Dogs ; Hypertension ; metabolism ; Kidney ; innervation ; surgery ; Phosphopyruvate Hydratase ; metabolism ; S100 Calcium Binding Protein beta Subunit ; metabolism ; Sympathectomy

Objective:To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT).Methods:A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD 2Gy), they were divided into the 30-39 Gy group ( n= 104) and ≥40 Gy group ( n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results:The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis: the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%( P=0.430) and 41.1% and 46.4%( P=0.068), respectively. Multivariate survival analysis: different doses of WBRT were not associated with the improvement of iPFS and OS; independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy; independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis: in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40 Gy were seemingly better than those of their counterparts with 30-39 Gy, but the difference was statistically significant only in OS ( P=0.047), the difference was not statistically significant in iPFS ( P=0.068); in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40 Gy were better than those of their counterparts with 30-39 Gy ( P=0.017, P=0.012); in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40 Gy group were better than those in the 30-39 Gy group ( P=0.012, P=0.045). Conclusions:The 30-39 Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40 Gy does not bring more benefits. WBRT≥40 Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.

Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment